Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin.

Hoadley KA1, Yau C2, Wolf DM3, Cherniack AD4, Tamborero D5, Ng S6, Leiserson MD7, Niu B8, McLellan MD8, Uzunangelov V6, Zhang J9, Kandoth C8, Akbani R10, Shen H11, Omberg L12, Chu A13, Margolin AA12, Van't Veer LJ3, Lopez-Bigas N14, Laird PW11, Raphael BJ7, Ding L8, Robertson AG13, Byers LA10, Mills GB10, Weinstein JN10, Van Waes C15, Chen Z16, Collisson EA17; Cancer Genome Atlas Research Network, Benz CC18, Perou CM19, Stuart JM20.

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Abstract

Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.